TABLE 1.
Comparison of trans-lactam potency in rVV NS3-5 gel-based assay and ELISA using antibodies of different specificitiesa
| Compound IDb | Gel-based assay end pointc (μM) | ELISA IC50 (μM) ± SEd
|
Vero cell CC50 (μM) | Selectivity indexg | |
|---|---|---|---|---|---|
| Anti-C100 antibodye | Anti-NS5A antibodyf | ||||
| 1c | <0.3 | <1.6 | 0.4 ± 0.1 | 124 | >78 |
| 1d | 1 | 1.2 ± 0.7 | 0.3 ± 0.2 | 144 | 120 |
| 1e | <0.3 | 2.1 ± 0.1 | NT | 76 | 36 |
| 1f | 1 | 4.6 ± 0.4 | 5.2 ± 0.6 | 78 | 17 |
| 1g | 1 | 5.9 ± 0.6 | 5.4 ± 0.3 | 270 | 46 |
| 1h | 1 | NT | 6.1 ± 0.6 | 95 | 16h |
| 1i | 3 | 7.8 ± 0.7 | NT | 382 | 49 |
| 1j | 3 | 9.0 ± 1.4 | NT | 320 | 36 |
| 1k | 1 | 9.1 ± 0.7 | 8.0 ± 0.6 | 290 | 32 |
| 1a | 3 | 11.8 ± 0.7 | 8.3 ± 0.4 | 92 | 8 |
| 1l | 3 | NT | 13.4 ± 0.9 | 279 | 21h |
| 1m | 3 | NT | 15.1 ± 0.7 | >500 | >33h |
| 1n | 3-10 | NT | 20.3 ± 2.6 | 331 | 16h |
| 1o | 3-10 | 67.9 | >100 | 500 | 7 |
| 4 | 3 | >100 | >100 | >500 | NC |
| 1p | 10 | >100 | 23.4 ± 2.2 | 531 | NC |
| 1q | >10 | >100 | 50.7 ± 13.7 | >500 | NC |
a
Results are ranked according to data from the ELISA using the anti-C100 antibody.
b
ID, identification number.
c
Defined as the lowest concentration at which NS4B is no longer visible.
d
Standard errors were derived from a GraFit software program used to calculate IC50. Compounds were tested once. NT, not tested.
e
8958, from Biogenesis (see Materials and Methods).
f
8808, from Biogenesis (see Materials and Methods).
g
Calculated by dividing the Vero cell CC50 by the ELISA IC50 (anti-C100 antibody). NC, not calculated.
h
Calculated by using the anti-NS5A antibody result.